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155. Fat Mass and Obesity-Associated Gene (FTO) in Eating Disorders: Evidence for Association of the rs9939609 Obesity Risk Allele with Bulimia nervosa and Anorexia nervosa

Author

Müller, Timo D., Greene, Brandon H., Bellodi, Laura, Cavallini, Maria C., Cellini, Elena, Di Bella, Daniela, Ehrlich, Stefan, Erzegovesi, Stefano, Estivill, Xavier, Fernández-Aranda, Fernando, Fichter, Manfred, Fleischhaker, Christian, Scherag, Susann, Gratacòs, Monica, Grallert, Harald, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Illig, Thomas, Lehmkuhl, Ulrike, Nacmias, Benedetta, Ribasés, Marta, Ricca, Valdo, Schäfer, Helmut, Scherag, André, Sorbi, Sandro, Wichmann, Heinz-Erich, Hebebrand, Johannes, and Hinney, Anke

Published
2012
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156. Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies

Author

Grallert, Harald, Dupuis, Josée, Bis, Joshua C., Dehghan, Abbas, Barbalic, Maja, Baumert, Jens, Lu, Chen, Smith, Nicholas L., Uitterlinden, André G., Roberts, Robert, Khuseyinova, Natalie, Schnabel, Renate B., Rice, Kenneth M., Rivadeneira, Fernando, Hoogeveen, Ron C., Fontes, João Daniel, Meisinger, Christa, Keaney, John F., Jr., Lemaitre, Rozenn, Aulchenko, Yurii S., Vasan, Ramachandran S., Ellis, Stephen, Hazen, Stanley L., van Duijn, Cornelia M., Nelson, Jeanenne J., März, Winfried, Schunkert, Heribert, McPherson, Ruth M., Stirnadel-Farrant, Heide A., Psaty, Bruce M., Gieger, Christian, Siscovick, David, Hofman, Albert, Illig, Thomas, Cushman, Mary, Yamamoto, Jennifer F., Rotter, Jerome I., Larson, Martin G., Stewart, Alexandre F.R., Boerwinkle, Eric, Witteman, Jacqueline C.M., Tracy, Russell P., Koenig, Wolfgang, Benjamin, Emelia J., and Ballantyne, Christie M.

Published
2012
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159. Genetic studies of leptin concentrations implicate leptin in the regulation of early adiposity

Author

Admin, Ada, primary, Yaghootkar, Hanieh, primary, Zhang, Yiying, primary, Spracklen, Cassandra N, primary, Karaderi, Tugce, primary, Huang, Lam Opal, primary, Bradfield, Jonathan, primary, Schurmann, Claudia, primary, Fine, Rebecca S, primary, Preuss, Michael H, primary, Kutalik, Zoltan, primary, Wittemans, Laura BL, primary, Lu, Yingchang, primary, Metz, Sophia, primary, Willems, Sara M, primary, Li-Gao, Ruifang, primary, Grarup, Niels, primary, Wang, Shuai, primary, Molnos, Sophie, primary, Sandoval-Zárate, América A, primary, Nalls, Mike A, primary, Lange, Leslie A, primary, Haesser, Jeffrey, primary, Guo, Xiuqing, primary, Lyytikäinen, Leo-Pekka, primary, Feitosa, Mary F, primary, Sitlani, Colleen M, primary, Venturini, Cristina, primary, Mahajan, Anubha, primary, Kacprowski, Tim, primary, Wang, Carol A, primary, Chasman, Daniel I, primary, Amin, Najaf, primary, Broer, Linda, primary, Robertson, Neil, primary, Young, Kristin L, primary, Allison, Matthew, primary, Blüher, Matthias, primary, Borja, Judith B, primary, Bork-Jensen, Jette, primary, Carrasquilla, Germán D, primary, Christofidou, Paraskevi, primary, Demirkan, Ayse, primary, Doege, Claudia A, primary, Garcia, Melissa E, primary, Graff, Mariaelisa, primary, Guo, Kaiying, primary, Hakonarson, Hakon, primary, Hong, Jaeyoung, primary, Chen, Yii-Der Ida, primary, Jackson, Rebecca, primary, Jakupović, Hermina, primary, Jousilahti, Pekka, primary, Justice, Anne E, primary, Kähönen, Mika, primary, Kizer, Jorge R, primary, Kriebe, Jennifer, primary, LeDuc, Charles A, primary, Li, Jin, primary, Lind, Lars, primary, Luan, Jian’an, primary, Mackey, David, primary, Mangino, Massimo, primary, Männistö, Satu, primary, Carli, Jayne F Martin, primary, Medina-Gomez, Carolina, primary, Mook-Kanamori, Dennis O, primary, Morris, Andrew P, primary, Mutsert, Renée de, primary, Nauck, Matthias, primary, Nedeljkovic, Ivana, primary, Pennell, Craig E, primary, Pradhan, Arund D, primary, Psaty, Bruce M, primary, Raitakari, Olli T, primary, Scott, Robert A, primary, Skaaby, Tea, primary, Strauch, Konstantin, primary, Taylor, Kent D, primary, Teumer, Alexander, primary, Uitterlinden, Andre G, primary, Wu, Ying, primary, Yao, Jie, primary, Walker, Mark, primary, North, Kari E, primary, Kovacs, Peter, primary, Ikram, M. Arfan, primary, Duijn, Cornelia M van, primary, Ridker, Paul M, primary, Lye, Stephen, primary, Homuth, Georg, primary, Ingelsson, Erik, primary, Spector, Tim D, primary, McKnight, Barbara, primary, Province, Michael A, primary, Lehtimäki, Terho, primary, Adair, Linda S, primary, Rotter, Jerome I, primary, Reiner, Alexander P, primary, Wilson, James G, primary, Harris, Tamara B, primary, Ripatti, Samuli, primary, Grallert, Harald, primary, Meigs, James B, primary, Salomaa, Veikko, primary, Hansen, Torben, primary, Dijk, Ko Willems van, primary, Wareham, Nicholas J, primary, Grant, Struan FA, primary, Langenberg, Claudia, primary, Frayling, Timothy M, primary, Lindgren, Cecilia M, primary, Mohlke, Karen L, primary, Leibel, Rudolph L, primary, Loos, Ruth JF, primary, and Kilpeläinen, Tuomas O, primary

Published
2020
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161. Deciphering the Plasma Proteome of Type 2 Diabetes

Author

Admin, Ada, primary, Elhadad, Mohamed A., primary, Jonasson, Christian, primary, Huth, Cornelia, primary, Wilson, Rory, primary, Gieger, Christian, primary, Matias, Pamela, primary, Grallert, Harald, primary, Graumann, Johannes, primary, Gailus-Durner, Valerie, primary, Rathmann, Wolfgang, primary, Toerne, Christine von, primary, Hauck, Stefanie M., primary, Koenig, Wolfgang, primary, Sinner, Moritz F., primary, Oprea, Tudor I, primary, Suhre, Karsten, primary, Thorand, Barbara, primary, Hveem, Kristian, primary, Peters, Annette, primary, and Waldenberger, Melanie, primary

Published
2020
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162. Deciphering the Plasma Proteome of Type 2 Diabetes

Author

Elhadad, Mohamed A., primary, Jonasson, Christian, additional, Huth, Cornelia, additional, Wilson, Rory, additional, Gieger, Christian, additional, Matias, Pamela, additional, Grallert, Harald, additional, Graumann, Johannes, additional, Gailus-Durner, Valerie, additional, Rathmann, Wolfgang, additional, von Toerne, Christine, additional, Hauck, Stefanie M., additional, Koenig, Wolfgang, additional, Sinner, Moritz F., additional, Oprea, Tudor I., additional, Suhre, Karsten, additional, Thorand, Barbara, additional, Hveem, Kristian, additional, Peters, Annette, additional, and Waldenberger, Melanie, additional

Published
2020
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163. Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity

Author

Yaghootkar, Hanieh, primary, Zhang, Yiying, additional, Spracklen, Cassandra N., additional, Karaderi, Tugce, additional, Huang, Lam Opal, additional, Bradfield, Jonathan, additional, Schurmann, Claudia, additional, Fine, Rebecca S., additional, Preuss, Michael H., additional, Kutalik, Zoltan, additional, Wittemans, Laura B.L., additional, Lu, Yingchang, additional, Metz, Sophia, additional, Willems, Sara M., additional, Li-Gao, Ruifang, additional, Grarup, Niels, additional, Wang, Shuai, additional, Molnos, Sophie, additional, Sandoval-Zárate, América A., additional, Nalls, Mike A., additional, Lange, Leslie A., additional, Haesser, Jeffrey, additional, Guo, Xiuqing, additional, Lyytikäinen, Leo-Pekka, additional, Feitosa, Mary F., additional, Sitlani, Colleen M., additional, Venturini, Cristina, additional, Mahajan, Anubha, additional, Kacprowski, Tim, additional, Wang, Carol A., additional, Chasman, Daniel I., additional, Amin, Najaf, additional, Broer, Linda, additional, Robertson, Neil, additional, Young, Kristin L., additional, Allison, Matthew, additional, Auer, Paul L., additional, Blüher, Matthias, additional, Borja, Judith B., additional, Bork-Jensen, Jette, additional, Carrasquilla, Germán D., additional, Christofidou, Paraskevi, additional, Demirkan, Ayse, additional, Doege, Claudia A., additional, Garcia, Melissa E., additional, Graff, Mariaelisa, additional, Guo, Kaiying, additional, Hakonarson, Hakon, additional, Hong, Jaeyoung, additional, Ida Chen, Yii-Der, additional, Jackson, Rebecca, additional, Jakupović, Hermina, additional, Jousilahti, Pekka, additional, Justice, Anne E., additional, Kähönen, Mika, additional, Kizer, Jorge R., additional, Kriebel, Jennifer, additional, LeDuc, Charles A., additional, Li, Jin, additional, Lind, Lars, additional, Luan, Jian’an, additional, Mackey, David A., additional, Mangino, Massimo, additional, Männistö, Satu, additional, Martin Carli, Jayne F., additional, Medina-Gomez, Carolina, additional, Mook-Kanamori, Dennis O., additional, Morris, Andrew P., additional, de Mutsert, Renée, additional, Nauck, Matthias, additional, Prokic, Ivana, additional, Pennell, Craig E., additional, Pradhan, Arund D., additional, Psaty, Bruce M., additional, Raitakari, Olli T., additional, Scott, Robert A., additional, Skaaby, Tea, additional, Strauch, Konstantin, additional, Taylor, Kent D., additional, Teumer, Alexander, additional, Uitterlinden, Andre G., additional, Wu, Ying, additional, Yao, Jie, additional, Walker, Mark, additional, North, Kari E., additional, Kovacs, Peter, additional, Ikram, M. Arfan, additional, van Duijn, Cornelia M., additional, Ridker, Paul M., additional, Lye, Stephen, additional, Homuth, Georg, additional, Ingelsson, Erik, additional, Spector, Tim D., additional, McKnight, Barbara, additional, Province, Michael A., additional, Lehtimäki, Terho, additional, Adair, Linda S., additional, Rotter, Jerome I., additional, Reiner, Alexander P., additional, Wilson, James G., additional, Harris, Tamara B., additional, Ripatti, Samuli, additional, Grallert, Harald, additional, Meigs, James B., additional, Salomaa, Veikko, additional, Hansen, Torben, additional, Willems van Dijk, Ko, additional, Wareham, Nicholas J., additional, Grant, Struan F.A., additional, Langenberg, Claudia, additional, Frayling, Timothy M., additional, Lindgren, Cecilia M., additional, Mohlke, Karen L., additional, Leibel, Rudolph L., additional, Loos, Ruth J.F., additional, and Kilpeläinen, Tuomas O., additional

Published
2020
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164. Arrhythmic Gut Microbiome Signatures Predict Risk of Type 2 Diabetes

Author

Reitmeier, Sandra, primary, Kiessling, Silke, additional, Clavel, Thomas, additional, List, Markus, additional, Almeida, Eduardo L., additional, Ghosh, Tarini S., additional, Neuhaus, Klaus, additional, Grallert, Harald, additional, Linseisen, Jakob, additional, Skurk, Thomas, additional, Brandl, Beate, additional, Breuninger, Taylor A., additional, Troll, Martina, additional, Rathmann, Wolfgang, additional, Linkohr, Birgit, additional, Hauner, Hans, additional, Laudes, Matthias, additional, Franke, Andre, additional, Le Roy, Caroline I., additional, Bell, Jordana T., additional, Spector, Tim, additional, Baumbach, Jan, additional, O’Toole, Paul W., additional, Peters, Annette, additional, and Haller, Dirk, additional

Published
2020
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165. The Trans-Ancestral Genomic Architecture of Glycaemic Traits

Author

Chen, Ji, primary, Spracklen, Cassandra N., additional, Marenne, Gaëlle, additional, Varshney, Arushi, additional, Corbin, Laura J, additional, Luan, Jian’an, additional, Willems, Sara, additional, Wu, Ying, additional, Zhang, Xiaoshuai, additional, Horikoshi, Momoko, additional, Boutin, Thibaud S, additional, Mägi, Reedik, additional, Waage, Johannes, additional, Pitsilides, Achilleas, additional, Li-Gao, Ruifang, additional, Hang, Kei, additional, Yao, Jie, additional, Anasanti, Mila D, additional, Chu, Audrey Y, additional, Claringbould, Annique, additional, Heikkinen, Jani, additional, Hong, Jaeyoung, additional, Hottenga, Jouke-Jan, additional, Huo, Shaofeng, additional, Kaakinen, Marika A., additional, Louie, Tin, additional, März, Winfried, additional, Moreno-Macias, Hortensia, additional, Ndungu, Anne, additional, Nelson, Sarah C., additional, Nolte, Ilja M., additional, North, Kari, additional, Raulerson, Chelsea K., additional, Ray, Debashree, additional, Rohde, Rebecca, additional, Rybin, Denis, additional, Schurmann, Claudia, additional, Sim, Xueling, additional, Southam, Loz, additional, Stewart, Isobel, additional, Wang, Carol A., additional, Wang, Yujie, additional, Wu, Peitao, additional, Zhang, Weihua, additional, Ahluwalia, Tarunveer S., additional, Appel, Emil VR, additional, Bielak, Lawrence F., additional, Brody, Jennifer A., additional, Burtt, Noel P, additional, Cabrera, Claudia P, additional, Cade, Brian E, additional, Chai, Jin Fang, additional, Chai, Xiaoran, additional, Chang, Li-Ching, additional, Chen, Chien-Hsiun, additional, Chen, Brian H, additional, Chitrala, Kumaraswamy N, additional, Chiu, Yen-Feng, additional, de Haan, Hugoline G., additional, Delgado, Graciela E, additional, Demirkan, Ayse, additional, Duan, Qing, additional, Engmann, Jorgen, additional, Fatumo, Segun A, additional, Gayán, Javier, additional, Giulianini, Franco, additional, Gong, Jung Ho, additional, Gustafsson, Stefan, additional, Hai, Yang, additional, Hartwig, Fernando P, additional, He, Jing, additional, Heianza, Yoriko, additional, Huang, Tao, additional, Huerta-Chagoya, Alicia, additional, Hwang, Mi Yeong, additional, Jensen, Richard A., additional, Kawaguchi, Takahisa, additional, Kentistou, Katherine A, additional, Kim, Young Jin, additional, Kleber, Marcus E, additional, Kooner, Ishminder K, additional, Lai, Shuiqing, additional, Lange, Leslie A, additional, Langefeld, Carl D, additional, Lauzon, Marie, additional, Li, Man, additional, Ligthart, Symen, additional, Liu, Jun, additional, Loh, Marie, additional, Long, Jirong, additional, Lyssenko, Valeriya, additional, Mangino, Massimo, additional, Marzi, Carola, additional, Montasser, May E, additional, Nag, Abhishek, additional, Nakatochi, Masahiro, additional, Noce, Damia, additional, Noordam, Raymond, additional, Pistis, Giorgio, additional, Preuss, Michael, additional, Raffield, Laura, additional, Rasmussen-Torvik, Laura J., additional, Rich, Stephen S, additional, Robertson, Neil R, additional, Rueedi, Rico, additional, Ryan, Kathleen, additional, Sanna, Serena, additional, Saxena, Richa, additional, Schraut, Katharina E, additional, Sennblad, Bengt, additional, Setoh, Kazuya, additional, Smith, Albert V, additional, Southam, Lorraine, additional, Sparsø, Thomas, additional, Strawbridge, Rona J, additional, Takeuchi, Fumihiko, additional, Tan, Jingyi, additional, Trompet, Stella, additional, van den Akker, Erik, additional, Van der Most, Peter J, additional, Verweij, Niek, additional, Vogel, Mandy, additional, Wang, Heming, additional, Wang, Chaolong, additional, Wang, Nan, additional, Warren, Helen R, additional, Wen, Wanqing, additional, Wilsgaard, Tom, additional, Wong, Andrew, additional, Wood, Andrew R, additional, Xie, Tian, additional, Zafarmand, Mohammad Hadi, additional, Zhao, Jing-Hua, additional, Zhao, Wei, additional, Amin, Najaf, additional, Arzumanyan, Zorayr, additional, Astrup, Arne, additional, Bakker, Stephan JL, additional, Baldassarre, Damiano, additional, Beekman, Marian, additional, Bergman, Richard N, additional, Bertoni, Alain, additional, Blüher, Matthias, additional, Bonnycastle, Lori L., additional, Bornstein, Stefan R, additional, Bowden, Donald W, additional, Cai, Qiuyin, additional, Campbell, Archie, additional, Campbell, Harry, additional, Chang, Yi Cheng, additional, de Geus, Eco J.C., additional, Dehghan, Abbas, additional, Du, Shufa, additional, Eiriksdottir, Gudny, additional, Farmaki, Aliki Eleni, additional, Frånberg, Mattias, additional, Fuchsberger, Christian, additional, Gao, Yutang, additional, Gjesing, Anette P, additional, Goel, Anuj, additional, Han, Sohee, additional, Hartman, Catharina A, additional, Herder, Christian, additional, Hicks, Andrew A., additional, Hsieh, Chang-Hsun, additional, Hsueh, Willa A., additional, Ichihara, Sahoko, additional, Igase, Michiya, additional, Ikram, M. Arfan, additional, Johnson, W. Craig, additional, Jørgensen, Marit E, additional, Joshi, Peter K, additional, Kalyani, Rita R, additional, Kandeel, Fouad R., additional, Katsuya, Tomohiro, additional, Khor, Chiea Chuen, additional, Kiess, Wieland, additional, Kolcic, Ivana, additional, Kuulasmaa, Teemu, additional, Kuusisto, Johanna, additional, Läll, Kristi, additional, Lam, Kelvin, additional, Lawlor, Deborah A, additional, Lee, Nanette R., additional, Lemaitre, Rozenn N., additional, Li, Honglan, additional, Study, Lifelines Cohort, additional, Lin, Shih-Yi, additional, Lindström, Jaana, additional, Linneberg, Allan, additional, Liu, Jianjun, additional, Lorenzo, Carlos, additional, Matsubara, Tatsuaki, additional, Matsuda, Fumihiko, additional, Mingrone, Geltrude, additional, Mooijaart, Simon, additional, Moon, Sanghoon, additional, Nabika, Toru, additional, Nadkarni, Girish N., additional, Nadler, Jerry L., additional, Nelis, Mari, additional, Neville, Matthew J, additional, Norris, Jill M, additional, Ohyagi, Yasumasa, additional, Peters, Annette, additional, Peyser, Patricia A., additional, Polasek, Ozren, additional, Qi, Qibin, additional, Raven, Dennis, additional, Reilly, Dermot F, additional, Reiner, Alex, additional, Rivideneira, Fernando, additional, Roll, Kathryn, additional, Rudan, Igor, additional, Sabanayagam, Charumathi, additional, Sandow, Kevin, additional, Sattar, Naveed, additional, Schürmann, Annette, additional, Shi, Jinxiu, additional, Stringham, Heather M, additional, Taylor, Kent D., additional, Teslovich, Tanya M., additional, Thuesen, Betina, additional, Timmers, Paul RHJ, additional, Tremoli, Elena, additional, Tsai, Michael Y, additional, Uitterlinden, Andre, additional, van Dam, Rob M, additional, van Heemst, Diana, additional, van Hylckama Vlieg, Astrid, additional, Van Vliet-Ostaptchouk, Jana V, additional, Vangipurapu, Jagadish, additional, Vestergaard, Henrik, additional, Wang, Tao, additional, van Dijk, Ko Willems, additional, Xiang, Yongbing, additional, Zemunik, Tatijana, additional, Abecasis, Goncalo R, additional, Adair, Linda S., additional, Aguilar-Salinas, Carlos Alberto, additional, Alarcón-Riquelme, Marta E, additional, An, Ping, additional, Aviles-Santa, Larissa, additional, Becker, Diane M, additional, Beilin, Lawrence J, additional, Bergmann, Sven, additional, Bisgaard, Hans, additional, Black, Corri, additional, Boehnke, Michael, additional, Boerwinkle, Eric, additional, Böhm, Bernhard O, additional, Bønnelykke, Klaus, additional, Boomsma, D I., additional, Bottinger, Erwin P., additional, Buchanan, Thomas A, additional, Canouil, Mickaël, additional, Caulfield, Mark J, additional, Chambers, John C., additional, Chasman, Daniel I., additional, Chen, Yii-Der Ida, additional, Cheng, Ching-Yu, additional, Collins, Francis S., additional, Correa, Adolfo, additional, Cucca, Francesco, additional, de Silva, H. Janaka, additional, Dedoussis, George, additional, Elmståhl, Sölve, additional, Evans, Michele K., additional, Ferranni, Ele, additional, Ferruci, Luigi, additional, Florez, Jose C, additional, Franks, Paul, additional, Frayling, Timothy M, additional, Froguel, Philippe, additional, Gigante, Bruna, additional, Goodarzi, Mark O., additional, Gordon-Larsen, Penny, additional, Grallert, Harald, additional, Grarup, Niels, additional, Grimsgaard, Sameline, additional, Groop, Leif, additional, Gudnason, Vilmundur, additional, Guo, Xiuqing, additional, Hamsten, Anders, additional, Hansen, Torben, additional, Hayward, Caroline, additional, Heckbert, Susan R., additional, Horta, Bernardo L, additional, Huang, Wei, additional, Ingelsson, Erik, additional, James, Pankow S, additional, Jonas, Jost B, additional, Jukema, J. Wouter, additional, Kaleebu, Pontiano, additional, Kaplan, Robert, additional, Kardia, Sharon L.R., additional, Kato, Norihiro, additional, Keinanen-Kiukaanniemi, Sirkka M., additional, Kim, Bong-Jo, additional, Kivimaki, Mika, additional, Koistinen, Heikki A., additional, Kooner, Jaspal S., additional, Körner, Antje, additional, Kovacs, Peter, additional, Kuh, Diana, additional, Kumari, Meena, additional, Kutalik, Zoltan, additional, Laakso, Markku, additional, Lakka, Timo A., additional, Launer, Lenore J, additional, Leander, Karin, additional, Li, Huaixing, additional, Lin, Xu, additional, Lind, Lars, additional, Lindgren, Cecilia, additional, Liu, Simin, additional, Loos, Ruth J.F., additional, Magnusson, Patrik, additional, Mahajan, Anubha, additional, Metspalu, Andres, additional, Mook-Kanamori, Dennis O, additional, Mori, Trevor A, additional, Munroe, Patricia B, additional, Njølstad, Inger, additional, O’Connell, Jeffrey R, additional, Oldehinkel, Albertine J, additional, Ong, Ken K, additional, Padmanabhan, Sandosh, additional, Palmer, Colin N.A., additional, Palmer, Nicholette D, additional, Pedersen, Oluf, additional, Pennell, Craig E, additional, Porteous, David J, additional, Pramstaller, Peter P., additional, Province, Michael A., additional, Psaty, Bruce M., additional, Qi, Lu, additional, Raffel, Leslie J., additional, Rauramaa, Rainer, additional, Redline, Susan, additional, Ridker, Paul M, additional, Rosendaal, Frits R., additional, Saaristo, Timo E., additional, Sandhu, Manjinder, additional, Saramies, Jouko, additional, Schneiderman, Neil, additional, Schwarz, Peter, additional, Scott, Laura J., additional, Selvin, Elizabeth, additional, Sever, Peter, additional, Shu, Xiao-ou, additional, Slagboom, P Eline, additional, Small, Kerrin S, additional, Smith, Blair H, additional, Snieder, Harold, additional, Sofer, Tamar, additional, Sørensen, Thorkild I.A., additional, Spector, Tim D, additional, Stanton, Alice, additional, Steves, Claire J, additional, Stumvoll, Michael, additional, Sun, Liang, additional, Tabara, Yasuharu, additional, Tai, E Shyong, additional, Timpson, Nicholas J, additional, Tönjes, Anke, additional, Tuomilehto, Jaakko, additional, Tusie, Teresa, additional, Uusitupa, Matti, additional, van der Harst, Pim, additional, van Duijn, Cornelia, additional, Vitart, Veronique, additional, Vollenweider, Peter, additional, Vrijkotte, Tanja GM, additional, Wagenknecht, Lynne E, additional, Walker, Mark, additional, Wang, Ya X, additional, Wareham, Nick J, additional, Watanabe, Richard M, additional, Watkins, Hugh, additional, Wei, Wen B, additional, Wickremasinghe, Ananda R, additional, Willemsen, Gonneke, additional, Wilson, James F, additional, Wong, Tien-Yin, additional, Wu, Jer-Yuarn, additional, Xiang, Anny H, additional, Yanek, Lisa R, additional, Yengo, Loïc, additional, Yokota, Mitsuhiro, additional, Zeggini, Eleftheria, additional, Zheng, Wei, additional, Zonderman, Alan B, additional, Rotter, Jerome I, additional, Gloyn, Anna L, additional, McCarthy, Mark I., additional, Dupuis, Josée, additional, Meigs, James B, additional, Scott, Robert, additional, Prokopenko, Inga, additional, Leong, Aaron, additional, Liu, Ching-Ti, additional, Parker, Stephen CJ, additional, Mohlke, Karen L., additional, Langenberg, Claudia, additional, Wheeler, Eleanor, additional, Morris, Andrew P., additional, and Barroso, Inês, additional

Published
2020
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166. Elucidating the genetic risk of obesity through the human blood plasma proteome

Author

Zaghlool, Shaza B., primary, Sharma, Sapna, additional, Molnar, Megan, additional, Matías‐García, Pamela R., additional, Elhadad, Mohamed A., additional, Waldenberger, Melanie, additional, Peters, Annette, additional, Rathmann, Wolfgang, additional, Graumann, Johannes, additional, Gieger, Christian, additional, Grallert, Harald, additional, and Suhre, Karsten, additional

Published
2020
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167. Network reconstruction for trans acting genetic loci using multi-omics data and prior information

Author

Hawe, Johann S., primary, Saha, Ashis, additional, Waldenberger, Melanie, additional, Kunze, Sonja, additional, Wahl, Simone, additional, Müller-Nurasyid, Martina, additional, Prokisch, Holger, additional, Grallert, Harald, additional, Herder, Christian, additional, Peters, Annette, additional, Strauch, Konstantin, additional, Theis, Fabian J., additional, Gieger, Christian, additional, Chambers, John, additional, Battle, Alexis, additional, and Heinig, Matthias, additional

Published
2020
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168. Investigation of Adiposity Measures and Operational Taxonomic unit (OTU) Data Transformation Procedures in Stool Samples from a German Cohort Study Using Machine Learning Algorithms

Author

Troll, Martina, primary, Brandmaier, Stefan, additional, Reitmeier, Sandra, additional, Adam, Jonathan, additional, Sharma, Sapna, additional, Sommer, Alice, additional, Bind, Marie-Abèle, additional, Neuhaus, Klaus, additional, Clavel, Thomas, additional, Adamski, Jerzy, additional, Haller, Dirk, additional, Peters, Annette, additional, and Grallert, Harald, additional

Published
2020
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169. Rare Variants in Specific Lysosomal Genes Are Associated With Parkinson's Disease

Author

Hopfner, Franziska, primary, Mueller, Stefanie H., additional, Szymczak, Silke, additional, Junge, Olaf, additional, Tittmann, Lukas, additional, May, Sandra, additional, Lohmann, Katja, additional, Grallert, Harald, additional, Lieb, Wolfgang, additional, Strauch, Konstantin, additional, Müller‐Nurasyid, Martina, additional, Berger, Klaus, additional, Schormair, Barbara, additional, Winkelmann, Juliane, additional, Mollenhauer, Brit, additional, Trenkwalder, Claudia, additional, Maetzler, Walter, additional, Berg, Daniela, additional, Kasten, Meike, additional, Klein, Christine, additional, Höglinger, Günter U., additional, Gasser, Thomas, additional, Deuschl, Günther, additional, Franke, André, additional, Krawczak, Michael, additional, Dempfle, Astrid, additional, and Kuhlenbäumer, Gregor, additional

Published
2020
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170. Abstract 21: Deciphering the Plasma Proteome of Type 2 Diabetes

Author

Elhadad, Mohamed A, primary, Jonasson, Christian, additional, Huth, Cornelia, additional, Wilson, Rory, additional, Thorand, Barbara, additional, Grallert, Harald, additional, Graumann, Johannes, additional, Rathmann, Wolfgang, additional, Koenig, Wolfgang, additional, Sinner, Moritz F, additional, Gieger, Christian, additional, Suhre, Karsten, additional, Hveem, Kristian, additional, Peters, Annette, additional, and Waldenberger, Melanie, additional

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2020
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171. Correction: Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy

Author

Esslinger, Ulrike, primary, Garnier, Sophie, additional, Korniat, Agathe, additional, Proust, Carole, additional, Kararigas, Georgios, additional, Müller-Nurasyid, Martina, additional, Empana, Jean-Philippe, additional, Morley, Michael P., additional, Perret, Claire, additional, Stark, Klaus, additional, Bick, Alexander G., additional, Prasad, Sanjay K., additional, Kriebel, Jennifer, additional, Li, Jin, additional, Tiret, Laurence, additional, Strauch, Konstantin, additional, O’Regan, Declan P., additional, Marguiles, Kenneth B., additional, Seidman, Jonathan G., additional, Boutouyrie, Pierre, additional, Lacolley, Patrick, additional, Jouven, Xavier, additional, Hengstenberg, Christian, additional, Komajda, Michel, additional, Hakonarson, Hakon, additional, Isnard, Richard, additional, Arbustini, Eloisa, additional, Grallert, Harald, additional, Cook, Stuart A., additional, Seidman, Christine E., additional, Regitz-Zagrosek, Vera, additional, Cappola, Thomas P., additional, Charron, Philippe, additional, Cambien, François, additional, and Villard, Eric, additional

Published
2020
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172. Arrhythmic Gut Microbiome Signatures for Risk Profiling of Type-2 Diabetes

Author

Reitmeier, Sandra, primary, Kiessling, Silke, additional, Clavel, Thomas, additional, List, Markus, additional, Almeida, Eduardo L., additional, Ghosh, Tarini, additional, Neuhaus, Klaus, additional, Grallert, Harald, additional, Troll, Martina, additional, Rathmann, Wolfgang, additional, Linkohr, Birgit, additional, Andre, Franke, additional, Le Roy, Caroline, additional, Bell, Jordana, additional, Spector, Timothy D., additional, Baumbach, Jan, additional, o'toole, paul, additional, Peters, Annette, additional, and Haller, Dirk, additional

Published
2020
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174. Arrhythmic gut microbiome signatures for risk profiling of Type-2 Diabetes

Author

Reitmeier, Sandra, primary, Kießling, Silke, additional, Clavel, Thomas, additional, List, Markus, additional, Almeida, Eduardo L., additional, Ghosh, Tarini S., additional, Neuhaus, Klaus, additional, Grallert, Harald, additional, Troll, Martina, additional, Rathmann, Wolfgang, additional, Linkohr, Birgit, additional, Franke, Andre, additional, Le Roy, Caroline I., additional, Bell, Jordana T., additional, Spector, Tim, additional, Baumbach, Jan, additional, O’Toole, Peter W., additional, Peters, Annette, additional, and Haller, Dirk, additional

Published
2019
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176. Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes

Author

Perry, John R.B., Weedon, Michael N., Langenberg, Claudia, Jackson, Anne U., Lyssenko, Valeriya, Sparsø, Thomas, Thorleifsson, Gudmar, Grallert, Harald, Ferrucci, Luigi, Maggio, Marcello, Paolisso, Giuseppe, Walker, Mark, Palmer, Colin N.A., Payne, Felicity, Young, Elizabeth, Herder, Christian, Narisu, Narisu, Morken, Mario A., Bonnycastle, Lori L., Owen, Katharine R., Shields, Beverley, Knight, Beatrice, Bennett, Amanda, Groves, Christopher J., Ruokonen, Aimo, Jarvelin, Marjo Riitta, Pearson, Ewan, Pascoe, Laura, Ferrannini, Ele, Bornstein, Stefan R., Stringham, Heather M., Scott, Laura J., Kuusisto, Johanna, Nilsson, Peter, Neptin, Malin, Gjesing, Anette P., Pisinger, Charlotta, Lauritzen, Torsten, Sandbaek, Annelli, Sampson, Mike, Zeggini, MAGIC Ele, Lindgren, Cecilia M., Steinthorsdottir, Valgerdur, Thorsteinsdottir, Unnur, Hansen, Torben, Schwarz, Peter, Illig, Thomas, Laakso, Markku, Stefansson, Kari, Morris, Andrew D., Groop, Leif, Pedersen, Oluf, Boehnke, Michael, Barroso, Inês, Wareham, Nicholas J., Hattersley, Andrew T., McCarthy, Mark I., and Frayling, Timothy M.

Published
2010

177. Parental origin of sequence variants associated with complex diseases

Author

Kong, Augustine, Steinthorsdottir, Valgerdur, Masson, Gisli, Thorleifsson, Gudmar, Sulem, Patrick, Besenbacher, Soren, Jonasdottir, Aslaug, Sigurdsson, Asgeir, Th. Kristinsson, Kari, Jonasdottir, Adalbjorg, Frigge, Michael L., Gylfason, Arnaldur, Olason, Pall I., Gudjonsson, Sigurjon A., Sverrisson, Sverrir, Stacey, Simon N., Sigurgeirsson, Bardur, Benediktsdottir, Kristrun R., Sigurdsson, Helgi, Jonsson, Thorvaldur, Benediktsson, Rafn, Olafsson, Jon H., Th. Johannsson, Oskar, Hreidarsson, Astradur B., Sigurdsson, Gunnar, Voight, Benjamin F., Scott, Laura J., Dina, Christian, Zeggini, Eleftheria, Huth, Cornelia, Aulchenko, Yurii S., Welch, Ryan P., McCulloch, Laura J., Ferreira, Teresa, Grallert, Harald, Amin, Najaf, Wu, Guanming, Willer, Cristen J., Raychaudhuri, Soumya, Purcell, Shaun, McCarroll, Steve A., Langenberg, Claudia, Hoffmann, Oliver M., Dupuis, Josée, Qi, Lu, Segrè, Ayellet V., van Hoek, Mandy, Navarro, Pau, Ardlie, Kristin, Balkau, Beverley, Bennett, Amanda J., Blagieva, Roza, Boerwinkle, Eric, Bonnycastle, Lori L., Boström, Kristina Bengtsson, Bravenboer, Bert, Bumpstead, Suzannah, Burtt, Noël P., Charpentier, Guillaume, Chines, Peter S., Cornelis, Marilyn, Couper, David J., Crawford, Gabe, Doney, Alex S. F., Elliott, Katherine S., Elliott, Amanda L., Erdos, Michael R., Fox, Caroline S., Franklin, Christopher S., Ganser, Martha, Gieger, Christian, Grarup, Niels, Green, Todd, Griffin, Simon, Groves, Christopher J., Guiducci, Candace, Hadjadj, Samy, Hassanali, Neelam, Herder, Christian, Isomaa, Bo, Jackson, Anne U., Johnson, Paul R. V., Jørgensen, Torben, Kao, Wen H. L., Klopp, Norman, Kraft, Peter, Kuusisto, Johanna, Lauritzen, Torsten, Li, Man, Lieverse, Alouisius, Lindgren, Cecilia M., Lyssenko, Valeriya, Marre, Michel, Meitinger, Thomas, Midthjell, Kristian, Morken, Mario A, Narisu, Narisu, Nilsson, Peter, Owen, Katharine R., Payne, Felicity, Perry, John R. B., Petersen, Ann-Kristin, Platou, Carl, Proença, Christine, Prokopenko, Inga, Rathmann, Wolfgang, William Rayner, N., Robertson, Neil R., Rocheleau, Ghislain, Roden, Michael, Sampson, Michael J., Saxena, Richa, Shields, Beverley M., Shrader, Peter, Smith, Nicholas, Sparsø, Thomas, Strassburger, Klaus, Stringham, Heather M., Sun, Qi, Swift, Amy J., Thorand, Barbara, Tichet, Jean, Tuomi, Tiinamaija, van Dam, Rob, van Herpt, Thijs, Walters, Bragi G., Weedon, Michael N., Witteman, Jacqueline, Bergman, Richard N., Cauchi, Stephane, Collins, Francis S., Gloyn, Anna L., Gyllensten, Ulf, Hansen, Torben, Hide, Winston A., Hitman, Graham A., Hofman, Albert, Hunter, David, Hveem, Kristian, Laakso, Markku, Mohlke, Karen L., Morris, Andrew D., Palmer, Colin N. A., Pramstaller, Peter P., Rudan, Igor, Sijbrands, Eric, Stein, Lincoln D., Tuomilehto, Jaakko, Uitterlinden, Andre, Walker, Mark, Wareham, Nicholas J., Watanabe, Richard M., Abecasis, Goncalo R., Barroso, Inês, Boehm, Bernhard O., Campbell, Harry, Daly, Mark J., Florez, Jose C., Frayling, Timothy M., Groop, Leif, Hattersley, Andrew T., Hu, Frank B., Meigs, James B., Morris, Andrew P., Pankow, James S., Pedersen, Oluf, Sladek, Rob, Thorsteinsdottir, Unnur, Wichmann, H.-Erich, Wilson, James F., Illig, Thomas, Froguel, Philippe, van Duijn, Cornelia M., Stefansson, Kari, Altshuler, David, Boehnke, Michael, McCarthy, Mark I., Ferguson-Smith, Anne C., and Gudbjartsson, Daniel F.

Published
2009
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178. Underlying Genetic Models of Inheritance in Established Type 2 Diabetes Associations

Author

Salanti, Georgia, Southam, Lorraine, Altshuler, David, Ardlie, Kristin, Barroso, Inês, Boehnke, Michael, Cornelis, Marilyn C., Frayling, Timothy M., Grallert, Harald, Grarup, Niels, Groop, Leif, Hansen, Torben, Hattersley, Andrew T., Hu, Frank B., Hveem, Kristian, Illig, Thomas, Kuusisto, Johanna, Laakso, Markku, Langenberg, Claudia, Lyssenko, Valeriya, McCarthy, Mark I., Morris, Andrew, Morris, Andrew D., Palmer, Colin N. A., Payne, Felicity, Platou, Carl G. P., Scott, Laura J., Voight, Benjamin F., Wareham, Nicholas J., Zeggini, Eleftheria, and Ioannidis, John P. A.

Published
2009

183. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author

Da Silva Couto Alves, Alexessander, De Silva, N. Maneka G., Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H. Rob, Warrington, Nicole M., Lewin, Alexandra M., Kaakinen, Marika, Cousminer, Diana L., Thiering, Elisabeth, Timpson, Nicholas J., Bond, Tom A., Lowry, Estelle, Brown, Christopher D., Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P., Geller, Frank, Speed, Doug, Coin, Lachlan J. M., Loh, Marie, Barton, Sheila J., Beilin, Lawrence J., Bisgaard, Hans, Bonnelykke, Klaus, Alili, Rohia, Hatoum, Ida J., Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clement, Karine, Claringbould, Annique A.J, Consortium, BIOS, van Duijin, Cornelia M., Moltchanova, Elena, Eriksson, Johan G., Elks, Cathy, Feenstra, Bjarke, Flexeder, Claudia, Franks, Stephen, Frayling, Timothy M., Freathy, Rachel M., Elliot, Paul, Widen, Elisabeth, Hakonarson, Hakon, Hattersley, Andrew T., Rodriguez, Alina, Banterle, Marco, Heinrich, Joachim, Heude, Barbara, Holloway, John W., Hofman, Albert, Hypponen, Elina, Inskip, Hazel, Kaplan, Lee M., Hedman, Asa K., Laara, Esa, Prokisch, Holger, Grallert, Harald, Lakka, Timo A., Lawlor, Debbie A., Melbye, Mads, Ahluwalia, Tarunveer S., Marinelli, Marcella, Millwood, Iona Y., Palmer, Lyle J., Pennell, Craig E., Perry, John R., Ring, Susan M., Savolainen, Markku J., Rivadeneira, Fernando, Standl, Marie, Sunyer, Jordi, Tiesler, Carla M.T, Uitterlinden, Andre G., Schierding, William, O'Sullivan, Justin M., Prokopenko, Inga, Herzig, Karl-Heinz, Smith, George Davey, O'Reilly, Paul, Felix, Janine F., Buxton, Jessica L., Blakemore, Alexandra L. F, Ong, Ken K., Jaddoe, Vincent W.V, Grant, Struan F.A, Sebert, Sylvain, McCarthy, Mark L., and Jarvelin, Marjo-Riitta

Abstract

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Published
2019

184. Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology

Author

Spracklen, Cassandra N, Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S, Kutalik, Zoltan, Preuss, Michael H, Lu, Yingchang, Wittemans, Laura BL, Adair, Linda S, Allison, Matthew, Amin, Najaf, Auer, Paul L, Bartz, Traci M, Blüher, Matthias, Boehnke, Michael, Borja, Judith B, Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I, Chen, Yii-Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M, Feitosa, Mary F, Garcia, Melissa E, Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B, Highland, Heather M, Hong, Jaeyoung, Ikram, M Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kähönen, Mika, Kizer, Jorge R, Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A, Lehtimäki, Terho, Li, Jin, Li-Gao, Ruifang, Lind, Lars, Luan, Jian'an, Lyytikäinen, Leo-Pekka, MacGregor, Stuart, Mackey, David A, Mahajan, Anubha, Mangino, Massimo, Männistö, Satu, McCarthy, Mark I, McKnight, Barbara, Medina-Gomez, Carolina, Meigs, James B, Molnos, Sophie, Mook-Kanamori, Dennis, Morris, Andrew P, de Mutsert, Renee, Nalls, Mike A, Nedeljkovic, Ivana, North, Kari E, Pennell, Craig E, Pradhan, Aruna D, Province, Michael A, Raitakari, Olli T, Raulerson, Chelsea K, Reiner, Alex P, Ridker, Paul M, Ripatti, Samuli, Roberston, Neil, Rotter, Jerome I, Salomaa, Veikko, Sandoval-Zárate, America A, Sitlani, Colleen M, Spector, Tim D, Strauch, Konstantin, Stumvoll, Michael, Taylor, Kent D, Thuesen, Betina, Tönjes, Anke, Uitterlinden, Andre G, Venturini, Cristina, Walker, Mark, Wang, Carol A, Wang, Shuai, Wareham, Nicholas J, Willems, Sara M, Willems van Dijk, Ko, Wilson, James G, Wu, Ying, Yao, Jie, Young, Kristin L, Langenberg, Claudia, and Frayling, Timothy M

Subjects
Adult, Male, obesity, Adolescent, Quantitative Trait Loci, Cardiovascular, Medical and Health Sciences, White People, lipids, Young Adult, 80 and over, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Exome, Polymorphism, Aetiology, Metabolic and endocrine, Aged, Nutrition, African Americans, Genetics & Heredity, genome-wide association study, adiponectin, Whites, Human Genome, Single Nucleotide, Hispanic or Latino, Middle Aged, Biological Sciences, cardio metabolic traits, Black or African American, Phenotype, Adipose Tissue, Female
Abstract

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2× 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1× 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

Published
2019

185. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

Author

Justice, Anne E, Karaderi, Tugce, Highland, Heather M, Young, Kristin L, Graff, Mariaelisa, Lu, Yingchang, Turcot, Valérie, Auer, Paul L, Fine, Rebecca S, Guo, Xiuqing, Schurmann, Claudia, Lempradl, Adelheid, Marouli, Eirini, Mahajan, Anubha, Winkler, Thomas W, Locke, Adam E, Medina-Gomez, Carolina, Esko, Tõnu, Vedantam, Sailaja, Giri, Ayush, Lo, Ken Sin, Alfred, Tamuno, Mudgal, Poorva, Ng, Maggie CY, Heard-Costa, Nancy L, Feitosa, Mary F, Manning, Alisa K, Willems, Sara M, Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S, Allison, Matthew, Amouyel, Philippe, Arzumanyan, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Caulfield, Mark J, Cesana, Giancarlo, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Collins, Francis S, Cook, James P, Cox, Amanda J, Crosslin, David S, Danesh, John, de Bakker, Paul IW, Denus, Simon de, Mutsert, Renée de, Dedoussis, George, Demerath, Ellen W, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Dörr, Marcus, Drenos, Fotios, Dubé, Marie-Pierre, Dunning, Alison M, Easton, Douglas F, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C, Fornage, Myriam, Fox, Caroline S, Franks, Paul W, Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Grove, Megan L, Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, and Hattersley, Andrew T

Subjects
Male, ReproGen Consortium, Cardiovascular, Medical and Health Sciences, EPIC-CVD Consortium, Body Mass Index, MAGIC Investigators, Gene Frequency, Risk Factors, Clinical Research, Genetics, Animals, Humans, Homeostasis, Body Fat Distribution, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Exome, Global Lipids Genetic Consortium, Obesity, Aetiology, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Metabolic and endocrine, Nutrition, CHD Exome+ Consortium, Waist-Hip Ratio, Prevention, Human Genome, Proteins, Genetic Variation, T2D-Genes Consortium, Biological Sciences, Lipids, GoT2D Genes Consortium, InterAct, Case-Control Studies, Drosophila, Female, ExomeBP Consortium, Genome-Wide Association Study, Biotechnology, Developmental Biology
Abstract

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF

Published
2019

186. Disentangling the genetics of lean mass

Author

Karasik, David, Zillikens, M Carola, Hsu, Yi-Hsiang, Aghdassi, Ali, Akesson, Kristina, Amin, Najaf, Barroso, Inês, Bennett, David A, Bertram, Lars, Bochud, Murielle, Borecki, Ingrid B, Broer, Linda, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Campos-Obando, Natalia, Cauley, Jane A, Cawthon, Peggy M, Chambers, John C, Chen, Zhao, Cho, Nam H, Choi, Hyung Jin, Chou, Wen-Chi, Cummings, Steven R, de Groot, Lisette CPGM, De Jager, Phillip L, Demuth, Ilja, Diatchenko, Luda, Econs, Michael J, Eiriksdottir, Gudny, Enneman, Anke W, Eriksson, Joel, Eriksson, Johan G, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Gieger, Christian, Grallert, Harald, Gudnason, Vilmundur, Lenore, Launer J, Hayward, Caroline, Hofman, Albert, Homuth, Georg, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Johnson, Toby, Biffar, Reiner, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O, Klopp, Norman, Kloth, Jacqueline SL, Koller, Daniel L, Kooner, Jaspal S, Kraus, William E, Kritchevsky, Stephen, Kutalik, Zoltán, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Lerch, Markus M, Lewis, Joshua R, Lill, Christina, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Livshits, Gregory, Ljunggren, Östen, Loos, Ruth JF, Lorentzon, Mattias, Luan, Jian'an, Luben, Robert N, Malkin, Ida, McGuigan, Fiona E, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Håkan, Mellström, Dan, Michaëlsson, Karl, Mitchell, Braxton D, Morris, Andrew P, Mosekilde, Leif, Nethander, Maria, Newman, Anne B, O'Connell, Jeffery R, Oostra, Ben A, Orwoll, Eric S, Palotie, Aarno, Peacock, Munro, and Perola, Markus

Subjects
Adult, Male, meta-analysis of genome-wide association studies, Adolescent, European Continental Ancestry Group, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Medical and Health Sciences, White People, Young Adult, Versicans, ADAMTS Proteins, Engineering, Electric Impedance, 80 and over, Genetics, Humans, 2.1 Biological and endogenous factors, Absorptiometry, Polymorphism, Aetiology, skeletal muscle, Aged, Extracellular Matrix Proteins, body composition, Nutrition & Dietetics, Prevention, Human Genome, RNA-Binding Proteins, Skeletal, Body Fluid Compartments, Single Nucleotide, Middle Aged, Photon, metabolic profile, body fat, Phenotype, Adipose Tissue, Melanocortin, Muscle, Female, Type 4, Receptor, Genome-Wide Association Study
Abstract

BackgroundLean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.ObjectivesTo determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.MethodsWe performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n=38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).ResultsSeven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.ConclusionsIn conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

Published
2019

187. Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration

Author

Wilman, Henry R., Parisinos, Constantinos A., Atabaki-Pasdar, Naeimeh, Kelly, Matt, Thomas, E. Louise, Neubauer, Stefan, Jennison, Christopher, Ehrhardt, Beate, Baum, Patrick, Schoelsch, Corinna, Freijer, Jan, Grempler, Rolf, Graefe-Mody, Ulrike, Hennige, Anita, Dings, Christiane, Lehr, Thorsten, Scherer, Nina, Sihinecich, Iryna, Pattou, Francois, Raverdi, Violeta, Caiazzo, Robert, Torres, Fanelly, Verkindt, Helene, Mari, Andrea, Tura, Andrea, Giorgino, Toni, Bizzotto, Roberto, Froguel, Philippe, Bonneford, Amelie, Canouil, Mickael, Dhennin, Veronique, Brorsson, Caroline, Brunak, Soren, De Masi, Federico, Gudmundsdóttir, Valborg, Pedersen, Helle, Banasik, Karina, Thomas, Cecilia, Sackett, Peter, Staerfeldt, Hans Henrik, Lundgaard, Agnete, Nilsson, Birgitte, Nielsen, Agnes, Mazzoni, Gianluca, Karaderi, Tugce, Rasmussen, Simon, Johansen, Joachim, Allesøe, Rosa, Fritsche, Andreas, Thorand, Barbara, Adamski, Jurek, Grallert, Harald, Haid, Mark, Sharma, Sapna, Troll, Martina, Adam, Jonathan, Ferrer, Jorge, Eriksen, Heather, Frost, Gary, Haussler, Ragna, Hong, Mun gwan, Schwenk, Jochen, Uhlen, Mathias, Nicolay, Claudia, Pavo, Imre, Steckel-Hamann, Birgit, Thomas, Melissa, Adragni, Kofi, Wu, Han, Hart, Leen't, Roderick, Slieker, van Leeuwen, Nienke, Dekkers, Koen, Frau, Francesca, Gassenhuber, Johann, Jablonka, Bernd, Musholt, Petra, Ruetten, Hartmut, Tillner, Joachim, Baltauss, Tania, Bernard Poenaru, Oana, de Preville, Nathalie, Rodriquez, Marianne, Arumugam, Manimozhiyan, Allin, Kristine, Engelbrechtsen, Line, Hansen, Torben, Hansen, Tue, Forman, Annemette, Jonsson, Anna, Pedersen, Oluf, Dutta, Avirup, Vogt, Josef, Vestergaard, Henrik, Laakso, Markku, Kokkola, Tarja, Kuulasmaa, Teemu, Franks, Paul, Giordano, Nick, and Pomares-Millan, Hugo

Subjects
Genome-wide association study, Magnetic resonance imaging, Metabolism, Iron, Genetics, Metabolic syndrome
Abstract

Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p

Published
2019

188. Correction: Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology

Author

Spracklen, Cassandra N., Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S., Kutalik, Zoltan, Preuss, Michael H., Lu, Yingchang, Wittemans, Laura B. L., Adair, Linda S., Allison, Matthew, Amin, Najaf, Auer, Paul L., Bartz, Traci M., Blüher, Matthias, Boehnke, Michael, Borja, Judith B., Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I., Chen, Yii-Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M., Feitosa, Mary F., Garcia, Melissa E., Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B., Highland, Heather M., Hong, Jaeyoung, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kähönen, Mika, Kizer, Jorge R., Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A., Lehtimäki, Terho, Li, Jin, Li-Gao, Ruifang, Lind, Lars, Luan, Jian'an, Lyytikäinen, Leo-Pekka, MacGregor, Stuart, Mackey, David A., Mahajan, Anubha, Mangino, Massimo, Männistö, Satu, McCarthy, Mark I., McKnight, Barbara, Medina-Gomez, Carolina, Meigs, James B., Molnos, Sophie, Mook-Kanamori, Dennis, Morris, Andrew P., de Mutsert, Renee, Nalls, Mike A., Nedeljkovic, Ivana, North, Kari E., Pennell, Craig E., Pradhan, Aruna D., Province, Michael A., Raitakari, Olli T., Raulerson, Chelsea K., Reiner, Alex P., Ridker, Paul M., Ripatti, Samuli, Roberston, Neil, Rotter, Jerome I., Salomaa, Veikko, Sandoval-Zárate, America A., Sitlani, Colleen M., Spector, Tim D., Strauch, Konstantin, Stumvoll, Michael, Taylor, Kent D., Thuesen, Betina, Tönjes, Anke, Uitterlinden, Andre G., Venturini, Cristina, Walker, Mark, Wang, Carol A., Wang, Shuai, Wareham, Nicholas J., Willems, Sara M., Willems van Dijk, Ko, Wilson, James G., Wu, Ying, Yao, Jie, Young, Kristin L., Langenberg, Claudia, Frayling, Timothy M., Kilpeläinen, Tuomas O., Lindgren, Cecilia M., Loos, Ruth J. F., and Mohlke, Karen L.

Subjects
SDG 3 - Good Health and Well-being
Published
2019

189. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author

Couto Alves, Alexessander, De Silva, N Maneka G, Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H Rob, Warrington, Nicole M, Lewin, Alexandra M, Kaakinen, Marika, Cousminer, Diana L, Thiering, Elisabeth, Timpson, Nicholas J, Bond, Tom A, Lowry, Estelle, Brown, Christopher D, Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P, Geller, Frank, Speed, Doug, Coin, Lachlan J M, Loh, Marie, Barton, Sheila J, Beilin, Lawrence J, Bisgaard, Hans, Bønnelykke, Klaus, Alili, Rohia, Hatoum, Ida J, Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clément, Karine, Claringbould, Annique A J, Van Duijn, Cornelia M, Moltchanova, Elena, Eriksson, Johan G, Elks, Cathy, Feenstra, Bjarke, Flexeder, Claudia, Franks, Stephen, Frayling, Timothy M, Freathy, Rachel M, Elliott, Paul, Widén, Elisabeth, Hakonarson, Hakon, Hattersley, Andrew T, Rodriguez, Alina, Banterle, Marco, Heinrich, Joachim, Heude, Barbara, Holloway, John W, Hofman, Albert, Hyppönen, Elina, Inskip, Hazel, Kaplan, Lee M, Hedman, Asa K, Läärä, Esa, Prokisch, Holger, Grallert, Harald, Lakka, Timo A, Lawlor, Debbie A, Melbye, Mads, Ahluwalia, Tarunveer S, Marinelli, Marcella, Millwood, Iona Y, Palmer, Lyle J, Pennell, Craig E, Perry, John R, Ring, Susan M, Savolainen, Markku J, Rivadeneira, Fernando, Standl, Marie, Sunyer, Jordi, Tiesler, Carla M T, Uitterlinden, Andre G, Schierding, William, O'Sullivan, Justin M, Prokopenko, Inga, Herzig, Karl-Heinz, Smith, George Davey, O'Reilly, Paul, Felix, Janine F, Buxton, Jessica L, Blakemore, Alexandra I F, Ong, Ken K, Jaddoe, Vincent W V, Grant, Struan F A, Sebert, Sylvain, McCarthy, Mark I, Järvelin, Marjo-Riitta, Erasmus MC other, Epidemiology, Internal Medicine, Pediatrics, Medical Research Council (MRC), Sovio, Ulla [0000-0002-0799-1105], Perry, John [0000-0001-6483-3771], Ong, Kenneth [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Warrington, Nicole M [0000-0003-4195-775X], Lewin, Alexandra M [0000-0003-0081-7582], Kaakinen, Marika [0000-0002-9228-0462], Cousminer, Diana L [0000-0001-8864-7893], Timpson, Nicholas J [0000-0002-7141-9189], Lowry, Estelle [0000-0002-4655-416X], Brown, Christopher D [0000-0002-3785-5008], Estivill, Xavier [0000-0002-0723-2256], Geller, Frank [0000-0002-9238-3269], Speed, Doug [0000-0002-0096-9765], Coin, Lachlan J M [0000-0002-4300-455X], Loh, Marie [0000-0003-3626-8466], Barton, Sheila J [0000-0003-4963-4242], Alili, Rohia [0000-0002-0158-4250], Schramm, Katharina [0000-0002-8809-3170], Charles, Marie-Aline [0000-0003-4025-4390], Claringbould, Annique A J [0000-0002-9201-6557], van Duijn, Cornelia M [0000-0002-2374-9204], Feenstra, Bjarke [0000-0003-1478-649X], Frayling, Timothy M [0000-0001-8362-2603], Freathy, Rachel M [0000-0003-4152-2238], Widén, Elisabeth [0000-0001-7108-2806], Hakonarson, Hakon [0000-0003-2814-7461], Rodriguez, Alina [0000-0003-1209-8802], Heude, Barbara [0000-0002-1565-1629], Holloway, John W [0000-0001-9998-0464], Hofman, Albert [0000-0002-9865-121X], Hyppönen, Elina [0000-0003-3670-9399], Inskip, Hazel [0000-0001-8897-1749], Kaplan, Lee M [0000-0002-6301-2696], Prokisch, Holger [0000-0003-2379-6286], Lakka, Timo A [0000-0002-9199-2871], Lawlor, Debbie A [0000-0002-6793-2262], Melbye, Mads [0000-0001-8264-6785], Ahluwalia, Tarunveer S [0000-0002-7464-3354], Marinelli, Marcella [0000-0002-5450-3960], Palmer, Lyle J [0000-0002-1628-3055], Pennell, Craig E [0000-0002-0937-6165], Perry, John R [0000-0001-6483-3771], Ring, Susan M [0000-0003-3103-9330], Savolainen, Markku J [0000-0002-2557-6423], Rivadeneira, Fernando [0000-0001-9435-9441], Sunyer, Jordi [0000-0002-2602-4110], Schierding, William [0000-0001-5659-2701], O'Sullivan, Justin M [0000-0003-2927-450X], Prokopenko, Inga [0000-0003-1624-7457], Smith, George Davey [0000-0002-1407-8314], Felix, Janine F [0000-0002-9801-5774], Ong, Ken K [0000-0003-4689-7530], Jaddoe, Vincent W V [0000-0003-2939-0041], Sebert, Sylvain [0000-0001-6681-6983], McCarthy, Mark I [0000-0002-4393-0510], and Järvelin, Marjo-Riitta [0000-0002-2149-0630]

Subjects
Adult, Male, Pharmacogenomic Variants, Quantitative Trait Loci, BLOOD-PRESSURE, 030209 endocrinology & metabolism, Polymorphism, Single Nucleotide, Body Mass Index, EARLY-LIFE, 03 medical and health sciences, AGE, Quantitative Trait, Heritable, 0302 clinical medicine, Humans, Genetic Predisposition to Disease, Longitudinal Studies, 030212 general & internal medicine, GENOME-WIDE ASSOCIATION, METABOLIC RISK, Growth Charts, FTO GENE, Child, Research Articles, Genetic Association Studies, Adaptor Proteins, Signal Transducing, 2. Zero hunger, Science & Technology, BIRTH COHORT, Intracellular Signaling Peptides and Proteins, nutritional and metabolic diseases, SciAdv r-articles, Infant, Human Genetics, Genomics, 3. Good health, Multidisciplinary Sciences, BODY-MASS INDEX, OBESITY, Science & Technology - Other Topics, Receptors, Leptin, ADIPOSITY, Female, biological, Research Article, Genome-Wide Association Study
Abstract

Longitudinal data find a new variant controlling BMI in infancy and reveal genetic differences between infant and adult BMI., Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Published
2019

192. Structural insights into conformational stability of both wild-type and mutant Insulin Receptor Gene

Author

Soremekun, Chisom, Jjingo, Daudi, Kateete, David, Nash, Oyekanmi, Grallert, Harald, Peters, Annette, Chikowore, Tinashe, Batini, Chiara, Soremekun, Opeyemi, and Fatumo, Segun

Abstract

Type 2 diabetes (T2D) poses a health challenge. It can lead to complications such as heart disease, hypertension, heart failure, and stroke. Factors like obesity and lack of activity can contribute to insulin resistance. The insulin receptor gene (INSR) is responsible for producing insulin receptors. When this gene malfunctions, it can contribute to the development of T2D.

Published
2024
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193. IL6 Gene Promoter Polymorphisms and Type 2 Diabetes: Joint Analysis of Individual Participantsʼ Data From 21 Studies

Author

Huth, Cornelia, Heid, Iris M., Vollmert, Caren, Gieger, Christian, Grallert, Harald, Wolford, Johanna K., Langer, Birgit, Thorand, Barbara, Klopp, Norman, Hamid, Yasmin H., Pedersen, Oluf, Hansen, Torben, Lyssenko, Valeriya, Groop, Leif, Meisinger, Christa, Döring, Angela, Löwel, Hannelore, Lieb, Wolfgang, Hengstenberg, Christian, Rathmann, Wolfgang, Martin, Stephan, Stephens, Jeffrey W., Ireland, Helen, Mather, Hugh, Miller, George J., Stringham, Heather M., Boehnke, Michael, Tuomilehto, Jaakko, Boeing, Heiner, Möhlig, Matthias, Spranger, Joachim, Pfeiffer, Andreas, Wernstedt, Ingrid, Niklason, Anders, López-Bermejo, Abel, Fernández-Real, José-Manuel, Hanson, Robert L., Gallart, Luis, Vendrell, Joan, Tsiavou, Anastasia, Hatziagelaki, Erifili, Humphries, Steve E., Wichmann, H.-Erich, Herder, Christian, and Illig, Thomas

Published
2006

194. Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology

Author

Spracklen, Cassandra N., Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S., Kutalik, Zoltan, Preuss, Michael H., Lu, Yingchang, Wittemans, Laura B. L., Adair, Linda S., Allison, Matthew, Amin, Najaf, Auer, Paul L., Bartz, Traci M., Blueher, Matthias, Boehnke, Michael, Borja, Judith B., Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I., Chen, Yii-Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M., Feitosa, Mary F., Garcia, Melissa E., Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B., Highland, Heather M., Hong, Jaeyoung, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kahonen, Mika, Kizer, Jorge R., Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A., Lehtimaki, Terho, Li, Jin, Li-Gao, Ruifang, Lind, Lars, Luan, Jian'an, Lyytikainen, Leo-Pekka, MacGregor, Stuart, Mackey, David A., Mahajan, Anubha, Mangino, Massimo, Mannisto, Satu, McCarthy, Mark I., McKnight, Barbara, Medina-Gomez, Carolina, Meigs, James B., Molnos, Sophie, Mook-Kanamori, Dennis, Morris, Andrew P., de Mutsert, Renee, Nalls, Mike A., Nedeljkovic, Ivana, North, Kari E., Pennell, Craig E., Pradhan, Aruna D., Province, Michael A., Raitakari, Olli T., Raulerson, Chelsea K., Reiner, Alex P., Ridker, Paul M., Ripatti, Samuli, Roberston, Neil, Rotter, Jerome I., Salomaa, Veikko, Sandoval-Zarate, America A., Sitlani, Colleen M., Spector, Tim D., Strauch, Konstantin, Stumvoll, Michael, Taylor, Kent D., Thuesen, Betina, Toenjes, Anke, Uitterlinden, Andre G., Venturini, Cristina, Walker, Mark, Wang, Carol A., Wang, Shuai, Wareham, Nicholas J., Willems, Sara M., van Dijk, Ko Willems, Wilson, James G., Wu, Ying, Yao, Jie, Young, Kristin L., Langenberg, Claudia, Frayling, Timothy M., Kilpelainen, Tuomas O., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., Spracklen, Cassandra N., Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S., Kutalik, Zoltan, Preuss, Michael H., Lu, Yingchang, Wittemans, Laura B. L., Adair, Linda S., Allison, Matthew, Amin, Najaf, Auer, Paul L., Bartz, Traci M., Blueher, Matthias, Boehnke, Michael, Borja, Judith B., Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I., Chen, Yii-Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M., Feitosa, Mary F., Garcia, Melissa E., Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B., Highland, Heather M., Hong, Jaeyoung, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kahonen, Mika, Kizer, Jorge R., Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A., Lehtimaki, Terho, Li, Jin, Li-Gao, Ruifang, Lind, Lars, Luan, Jian'an, Lyytikainen, Leo-Pekka, MacGregor, Stuart, Mackey, David A., Mahajan, Anubha, Mangino, Massimo, Mannisto, Satu, McCarthy, Mark I., McKnight, Barbara, Medina-Gomez, Carolina, Meigs, James B., Molnos, Sophie, Mook-Kanamori, Dennis, Morris, Andrew P., de Mutsert, Renee, Nalls, Mike A., Nedeljkovic, Ivana, North, Kari E., Pennell, Craig E., Pradhan, Aruna D., Province, Michael A., Raitakari, Olli T., Raulerson, Chelsea K., Reiner, Alex P., Ridker, Paul M., Ripatti, Samuli, Roberston, Neil, Rotter, Jerome I., Salomaa, Veikko, Sandoval-Zarate, America A., Sitlani, Colleen M., Spector, Tim D., Strauch, Konstantin, Stumvoll, Michael, Taylor, Kent D., Thuesen, Betina, Toenjes, Anke, Uitterlinden, Andre G., Venturini, Cristina, Walker, Mark, Wang, Carol A., Wang, Shuai, Wareham, Nicholas J., Willems, Sara M., van Dijk, Ko Willems, Wilson, James G., Wu, Ying, Yao, Jie, Young, Kristin L., Langenberg, Claudia, Frayling, Timothy M., Kilpelainen, Tuomas O., Lindgren, Cecilia M., Loos, Ruth J. F., and Mohlke, Karen L.

Abstract

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 x 10(-7)). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r(2) > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 x 10(-4)) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

Published
2019
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195. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

Author

Justice, Anne E., Karaderi, Tugce, Highland, Heather M., Young, Kristin L., Graff, Mariaelisa, Lu, Yingchang, Turcot, Valerie, Auer, Paul L., Fine, Rebecca S., Guo, Xiuqing, Schurmann, Claudia, Lempradl, Adelheid, Marouli, Eirini, Mahajan, Anubha, Winkler, Thomas W., Locke, Adam E., Medina-Gomez, Carolina, Esko, Tonu, Vedantam, Sailaja, Giri, Ayush, Lo, Ken Sin, Alfred, Tamuno, Mudgal, Poorva, Ng, Maggie C. Y., Heard-Costa, Nancy L., Feitosa, Mary F., Manning, Alisa K., Willems, Sara M., Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S., Allison, Matthew, Amouyel, Philippe, Arzumanyanm, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Broer, Linda, Burt, Amber A., Butterworth, Adam S., Caulfield, Markj, Cesana, Giancarlo, Chambers, John C., Chasman, Daniel, I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audreyy, Collins, Francis S., Cook, James P., Cox, Amanda J., Crosslin, David S., Danesh, John, de Bakker, Paul I. W., de Denus, Simon, de Mutsert, Renee, Dedoussis, George, Demerath, Ellen W., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Doerr, Marcus, Drenos, Fotios, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Fornage, Myriam, Fox, Caroline S., Franks, Paul W., Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Groves, Megan L., Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, Hattersley, Andrew T., Hayward, Caroline, Heid, Iris M., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Hung, Yi-Jen, Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jarvik, Gail P., Jia, Yucheng, Jorgensen, Torben, Jousilahti, Pekka, Justesen, Johanne M., Kahali, Bratati, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kovacs, Peter, Kraemer, Bernhard K., Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, La Nge, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lee, Wen-Jane, Lehtimaeki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, RuifangLi-Gao, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstroem, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Luan, Jian'an, Lyytikainen, Leo-Pekka, MacGregor, Stuart, Magi, Reedik, Mannisto, Satu, Marenne, Gaelle, Marten, Jonathan, Mascal, Nicholas G. D., McCarthy, Mark, I, Meidtner, Karina, Mihailov, Evelin, Moilanen, Leena, Moitry, Marie, Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Ntalla, Ioanna, Owen, Katharine R., Pedersen, Oluf, Peloso, Gina M., Pennell, Craig E., Perola, Markus, James, A., Perry, John R. B., Pers, Tune H., Ewing, Ailith, Polasek, Ozren, Rasheed, Asif, Raulerson, Chelsea K., Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Ridker, Paul M., Rivas, Manuel A., Robertson, Neil R., Robino, Antonietta, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo, Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Blair H., Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swart, Karin M. A., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Torres, Mina, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van Duijn, Cornelia M., Vanhala, Mauno, Varma, Rohit, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wareham, N. Icholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Verges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Zillikens, M. Carola, Rivadeneira, Fernando, Borecki, Ingrid B., Pospisilik, J. Andrew, Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, Mohlke, Karen L., Rotter, Jerome, I, Kutalik, Zoltan, Hirschhorn, Joel N., Cupples, L. Adrienne, Loos, Ruth J. F., North, Kari E., Lindgren, Cecilia M., O'Connell, Jeffrey R., Raitakari, Olli T., Lange, Leslie A., Uitterlinden, Andr G., Grove, Megan L., Masca, Nicholas G. D., Luan, Jianan, Wareham, Nicholas J., Esko, Tnu, De Bakker, Paul Iw, Caulfield, Mark J., Mller-Nurasyid, Martina, Justice, Anne E., Karaderi, Tugce, Highland, Heather M., Young, Kristin L., Graff, Mariaelisa, Lu, Yingchang, Turcot, Valerie, Auer, Paul L., Fine, Rebecca S., Guo, Xiuqing, Schurmann, Claudia, Lempradl, Adelheid, Marouli, Eirini, Mahajan, Anubha, Winkler, Thomas W., Locke, Adam E., Medina-Gomez, Carolina, Esko, Tonu, Vedantam, Sailaja, Giri, Ayush, Lo, Ken Sin, Alfred, Tamuno, Mudgal, Poorva, Ng, Maggie C. Y., Heard-Costa, Nancy L., Feitosa, Mary F., Manning, Alisa K., Willems, Sara M., Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S., Allison, Matthew, Amouyel, Philippe, Arzumanyanm, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Broer, Linda, Burt, Amber A., Butterworth, Adam S., Caulfield, Markj, Cesana, Giancarlo, Chambers, John C., Chasman, Daniel, I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audreyy, Collins, Francis S., Cook, James P., Cox, Amanda J., Crosslin, David S., Danesh, John, de Bakker, Paul I. W., de Denus, Simon, de Mutsert, Renee, Dedoussis, George, Demerath, Ellen W., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Doerr, Marcus, Drenos, Fotios, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Fornage, Myriam, Fox, Caroline S., Franks, Paul W., Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Groves, Megan L., Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, Hattersley, Andrew T., Hayward, Caroline, Heid, Iris M., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Hung, Yi-Jen, Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jarvik, Gail P., Jia, Yucheng, Jorgensen, Torben, Jousilahti, Pekka, Justesen, Johanne M., Kahali, Bratati, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kovacs, Peter, Kraemer, Bernhard K., Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, La Nge, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lee, Wen-Jane, Lehtimaeki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, RuifangLi-Gao, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstroem, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Luan, Jian'an, Lyytikainen, Leo-Pekka, MacGregor, Stuart, Magi, Reedik, Mannisto, Satu, Marenne, Gaelle, Marten, Jonathan, Mascal, Nicholas G. D., McCarthy, Mark, I, Meidtner, Karina, Mihailov, Evelin, Moilanen, Leena, Moitry, Marie, Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Ntalla, Ioanna, Owen, Katharine R., Pedersen, Oluf, Peloso, Gina M., Pennell, Craig E., Perola, Markus, James, A., Perry, John R. B., Pers, Tune H., Ewing, Ailith, Polasek, Ozren, Rasheed, Asif, Raulerson, Chelsea K., Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Ridker, Paul M., Rivas, Manuel A., Robertson, Neil R., Robino, Antonietta, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo, Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Blair H., Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swart, Karin M. A., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Torres, Mina, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van Duijn, Cornelia M., Vanhala, Mauno, Varma, Rohit, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wareham, N. Icholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Verges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Zillikens, M. Carola, Rivadeneira, Fernando, Borecki, Ingrid B., Pospisilik, J. Andrew, Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, Mohlke, Karen L., Rotter, Jerome, I, Kutalik, Zoltan, Hirschhorn, Joel N., Cupples, L. Adrienne, Loos, Ruth J. F., North, Kari E., Lindgren, Cecilia M., O'Connell, Jeffrey R., Raitakari, Olli T., Lange, Leslie A., Uitterlinden, Andr G., Grove, Megan L., Masca, Nicholas G. D., Luan, Jianan, Wareham, Nicholas J., Esko, Tnu, De Bakker, Paul Iw, Caulfield, Mark J., and Mller-Nurasyid, Martina

Abstract

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

Published
2019
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196. Erratum:Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology (The American Journal of Human Genetics (2019) 105(1) (15–28), (S0002929719301880), (10.1016/j.ajhg.2019.05.002))

Author

Spracklen, Cassandra N., Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S., Kutalik, Zoltan, Preuss, Michael H., Lu, Yingchang, Wittemans, Laura B.L., Adair, Linda S., Allison, Matthew, Amin, Najaf, Auer, Paul L., Bartz, Traci M., Blüher, Matthias, Boehnke, Michael, Borja, Judith B., Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I., Chen, Yii Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M., Feitosa, Mary F., Garcia, Melissa E., Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B., Highland, Heather M., Hong, Jaeyoung, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kähönen, Mika, Kizer, Jorge R., Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A., Lehtimäki, Terho, Li, Jin, Li-Gao, Ruifang, Lind, Lars, Luan, Jian'an, Lyytikäinen, Leo Pekka, MacGregor, Stuart, Mackey, David A., Mahajan, Anubha, Mangino, Massimo, Männistö, Satu, McCarthy, Mark I., McKnight, Barbara, Medina-Gomez, Carolina, Meigs, James B., Molnos, Sophie, Mook-Kanamori, Dennis, Morris, Andrew P., de Mutsert, Renee, Nalls, Mike A., Nedeljkovic, Ivana, North, Kari E., Pennell, Craig E., Pradhan, Aruna D., Province, Michael A., Raitakari, Olli T., Raulerson, Chelsea K., Reiner, Alex P., Ridker, Paul M., Ripatti, Samuli, Roberston, Neil, Rotter, Jerome I., Salomaa, Veikko, Sandoval-Zárate, America A., Sitlani, Colleen M., Spector, Tim D., Strauch, Konstantin, Stumvoll, Michael, Taylor, Kent D., Thuesen, Betina, Tönjes, Anke, Uitterlinden, Andre G., Venturini, Cristina, Walker, Mark, Wang, Carol A., Wang, Shuai, Wareham, Nicholas J., Willems, Sara M., Willems van Dijk, Ko, Wilson, James G., Wu, Ying, Yao, Jie, Young, Kristin L., Langenberg, Claudia, Frayling, Timothy M., Kilpeläinen, Tuomas O., Lindgren, Cecilia M., Loos, Ruth J.F., Mohlke, Karen L., Spracklen, Cassandra N., Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S., Kutalik, Zoltan, Preuss, Michael H., Lu, Yingchang, Wittemans, Laura B.L., Adair, Linda S., Allison, Matthew, Amin, Najaf, Auer, Paul L., Bartz, Traci M., Blüher, Matthias, Boehnke, Michael, Borja, Judith B., Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I., Chen, Yii Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M., Feitosa, Mary F., Garcia, Melissa E., Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B., Highland, Heather M., Hong, Jaeyoung, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kähönen, Mika, Kizer, Jorge R., Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A., Lehtimäki, Terho, Li, Jin, Li-Gao, Ruifang, Lind, Lars, Luan, Jian'an, Lyytikäinen, Leo Pekka, MacGregor, Stuart, Mackey, David A., Mahajan, Anubha, Mangino, Massimo, Männistö, Satu, McCarthy, Mark I., McKnight, Barbara, Medina-Gomez, Carolina, Meigs, James B., Molnos, Sophie, Mook-Kanamori, Dennis, Morris, Andrew P., de Mutsert, Renee, Nalls, Mike A., Nedeljkovic, Ivana, North, Kari E., Pennell, Craig E., Pradhan, Aruna D., Province, Michael A., Raitakari, Olli T., Raulerson, Chelsea K., Reiner, Alex P., Ridker, Paul M., Ripatti, Samuli, Roberston, Neil, Rotter, Jerome I., Salomaa, Veikko, Sandoval-Zárate, America A., Sitlani, Colleen M., Spector, Tim D., Strauch, Konstantin, Stumvoll, Michael, Taylor, Kent D., Thuesen, Betina, Tönjes, Anke, Uitterlinden, Andre G., Venturini, Cristina, Walker, Mark, Wang, Carol A., Wang, Shuai, Wareham, Nicholas J., Willems, Sara M., Willems van Dijk, Ko, Wilson, James G., Wu, Ying, Yao, Jie, Young, Kristin L., Langenberg, Claudia, Frayling, Timothy M., Kilpeläinen, Tuomas O., Lindgren, Cecilia M., Loos, Ruth J.F., and Mohlke, Karen L.

Abstract

(The American Journal of Human Genetics 105, 15–28; July 3, 2019) In the originally published version of this article, the effect sizes for the previously reported loci achieving exome-wide significance (indicated with asterisks in the table below) were incorrect. The table has now been corrected online, and the authors apologize for this error. [Table presented]

Published
2019

197. Association of alcohol consumption with allergic disease and asthma:a multi-centre Mendelian randomization analysis

Author

Skaaby, Tea, Kilpeläinen, Tuomas O., Taylor, Amy E, Mahendran, Yuvaraj, Wong, Andrew, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Trompet, Stella, Stott, David J, Flexeder, Claudia, Zhou, Ang, Brusselle, Guy, Sajjad, Ayesha, Lahousse, Lies, Tiemeier, Henning, Have, Christian Theil, Thuesen, Betina H, Kårhus, Line Lund, Møllehave, Line Tang, Leth-Møller, Katja Biering, Shabanzadeh, Daniel Mønsted, Gonzalez-Quintela, Arturo, Power, Chris, Hyppönen, Elina, Kuh, Diana, Hardy, Rebecca, Meitinger, Thomas, Jukema, J Wouter, Völker, Uwe, Nauck, Matthias, Völzke, Henry, Friedrich, Nele, Bonten, Tobias N, Noordam, Raymond, Mook-Kanamori, Dennis O, Tolstrup, Janne S., Taube, Christian, Peters, Annette, Grallert, Harald, Strauch, Konstantin, Schulz, Holger, Grarup, Niels, Hansen, Torben, Pedersen, Oluf, Burgess, Stephen, Munafò, Marcus R, Linneberg, Allan, Skaaby, Tea, Kilpeläinen, Tuomas O., Taylor, Amy E, Mahendran, Yuvaraj, Wong, Andrew, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Trompet, Stella, Stott, David J, Flexeder, Claudia, Zhou, Ang, Brusselle, Guy, Sajjad, Ayesha, Lahousse, Lies, Tiemeier, Henning, Have, Christian Theil, Thuesen, Betina H, Kårhus, Line Lund, Møllehave, Line Tang, Leth-Møller, Katja Biering, Shabanzadeh, Daniel Mønsted, Gonzalez-Quintela, Arturo, Power, Chris, Hyppönen, Elina, Kuh, Diana, Hardy, Rebecca, Meitinger, Thomas, Jukema, J Wouter, Völker, Uwe, Nauck, Matthias, Völzke, Henry, Friedrich, Nele, Bonten, Tobias N, Noordam, Raymond, Mook-Kanamori, Dennis O, Tolstrup, Janne S., Taube, Christian, Peters, Annette, Grallert, Harald, Strauch, Konstantin, Schulz, Holger, Grarup, Niels, Hansen, Torben, Pedersen, Oluf, Burgess, Stephen, Munafò, Marcus R, and Linneberg, Allan

Abstract

AIMS: To use the rs1229984 variant associated with alcohol consumption as an instrument for alcohol consumption to test the causality of the association of alcohol consumption with hay fever, asthma, allergic sensitization and serum total immunoglobulin (Ig)E.DESIGN: Observational and Mendelian randomization analyses using genetic variants as unbiased markers of exposure to estimate causal effects, subject to certain assumptions.SETTING: Europe.PARTICIPANTS: We included a total of 466 434 people aged 15-82 years from 17 population-based studies conducted from 1997 to 2015.MEASUREMENTS: The rs1229984 (ADH1B) was genotyped; alcohol consumption, hay fever and asthma were self-reported. Specific and total IgE were measured from serum samples.FINDINGS: Observational analyses showed that ever-drinking versus non-drinking, but not amount of alcohol intake, was positively associated with hay fever and inversely associated with asthma but not with allergic sensitization or serum total immunoglobulin (Ig)E. However, Mendelian randomization analyses did not suggest that the observational associations are causal. The causal odds ratio (OR) per genetically assessed unit of alcohol/week was an OR = 0.907 [95% confidence interval (CI) = 0.806, 1.019; P = 0.101] for hay fever, an OR = 0.897 (95% CI = 0.790, 1.019; P = 0.095) for asthma, an OR = 0.971 (95% CI = 0.804, 1.174; P = 0.763) for allergic sensitization and a 4.7% change (95% CI = -5.5%, 14.9%; P = 0.366) for total IgE.CONCLUSIONS: In observational analyses, ever-drinking versus not drinking was positively associated with hay fever and negatively associated with asthma. However, the Mendelian randomization results were not consistent with these associations being causal.

Published
2019

198. An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis.

Author

Liu, Jun, Liu, Jun, Carnero-Montoro, Elena, van Dongen, Jenny, Lent, Samantha, Nedeljkovic, Ivana, Ligthart, Symen, Tsai, Pei-Chien, Martin, Tiphaine C, Mandaviya, Pooja R, Jansen, Rick, Peters, Marjolein J, Duijts, Liesbeth, Jaddoe, Vincent WV, Tiemeier, Henning, Felix, Janine F, Willemsen, Gonneke, de Geus, Eco JC, Chu, Audrey Y, Levy, Daniel, Hwang, Shih-Jen, Bressler, Jan, Gondalia, Rahul, Salfati, Elias L, Herder, Christian, Hidalgo, Bertha A, Tanaka, Toshiko, Moore, Ann Zenobia, Lemaitre, Rozenn N, Jhun, Min A, Smith, Jennifer A, Sotoodehnia, Nona, Bandinelli, Stefania, Ferrucci, Luigi, Arnett, Donna K, Grallert, Harald, Assimes, Themistocles L, Hou, Lifang, Baccarelli, Andrea, Whitsel, Eric A, van Dijk, Ko Willems, Amin, Najaf, Uitterlinden, André G, Sijbrands, Eric JG, Franco, Oscar H, Dehghan, Abbas, Spector, Tim D, Dupuis, Josée, Hivert, Marie-France, Rotter, Jerome I, Meigs, James B, Pankow, James S, van Meurs, Joyce BJ, Isaacs, Aaron, Boomsma, Dorret I, Bell, Jordana T, Demirkan, Ayşe, van Duijn, Cornelia M, Liu, Jun, Liu, Jun, Carnero-Montoro, Elena, van Dongen, Jenny, Lent, Samantha, Nedeljkovic, Ivana, Ligthart, Symen, Tsai, Pei-Chien, Martin, Tiphaine C, Mandaviya, Pooja R, Jansen, Rick, Peters, Marjolein J, Duijts, Liesbeth, Jaddoe, Vincent WV, Tiemeier, Henning, Felix, Janine F, Willemsen, Gonneke, de Geus, Eco JC, Chu, Audrey Y, Levy, Daniel, Hwang, Shih-Jen, Bressler, Jan, Gondalia, Rahul, Salfati, Elias L, Herder, Christian, Hidalgo, Bertha A, Tanaka, Toshiko, Moore, Ann Zenobia, Lemaitre, Rozenn N, Jhun, Min A, Smith, Jennifer A, Sotoodehnia, Nona, Bandinelli, Stefania, Ferrucci, Luigi, Arnett, Donna K, Grallert, Harald, Assimes, Themistocles L, Hou, Lifang, Baccarelli, Andrea, Whitsel, Eric A, van Dijk, Ko Willems, Amin, Najaf, Uitterlinden, André G, Sijbrands, Eric JG, Franco, Oscar H, Dehghan, Abbas, Spector, Tim D, Dupuis, Josée, Hivert, Marie-France, Rotter, Jerome I, Meigs, James B, Pankow, James S, van Meurs, Joyce BJ, Isaacs, Aaron, Boomsma, Dorret I, Bell, Jordana T, Demirkan, Ayşe, and van Duijn, Cornelia M

Abstract

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.

Published
2019

199. Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology:[incl. correction]

Author

Spracklen, Cassandra N., Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S., Kutalik, Zoltan, Preuss, Michael H., Lu, Yingchang, Wittemans, Laura B.L., Adair, Linda S., Allison, Matthew, Amin, Najaf, Auer, Paul L., Bartz, Traci M., Blüher, Matthias, Boehnke, Michael, Borja, Judith B., Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I., Chen, Yii Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M., Feitosa, Mary F., Garcia, Melissa E., Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B., Highland, Heather M., Hong, Jaeyoung, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kähönen, Mika, Kizer, Jorge R., Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A., Lehtimäki, Terho, Li, Jin, Lind, Lars, Kilpeläinen, Tuomas O., Loos, Ruth J.F., Mohlke, Karen L, Spracklen, Cassandra N., Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S., Kutalik, Zoltan, Preuss, Michael H., Lu, Yingchang, Wittemans, Laura B.L., Adair, Linda S., Allison, Matthew, Amin, Najaf, Auer, Paul L., Bartz, Traci M., Blüher, Matthias, Boehnke, Michael, Borja, Judith B., Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I., Chen, Yii Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M., Feitosa, Mary F., Garcia, Melissa E., Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B., Highland, Heather M., Hong, Jaeyoung, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kähönen, Mika, Kizer, Jorge R., Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A., Lehtimäki, Terho, Li, Jin, Lind, Lars, Kilpeläinen, Tuomas O., Loos, Ruth J.F., and Mohlke, Karen L

Abstract

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10−7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10−4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

Published
2019

200. Mutation screen in the GWAS derived obesity gene SH2B1 including functional analyses of detected variants

Author

Volckmar Anna-Lena, Bolze Florian, Jarick Ivonne, Knoll Nadja, Scherag André, Reinehr Thomas, Illig Thomas, Grallert Harald, Wichmann Heinz-Erich, Wiegand Susanna, Biebermann Heike, Krude Heiko, Fischer-Posovszky Pamela, Rief Winfried, Wabitsch Martin, Klingenspor Martin, Hebebrand Johannes, and Hinney Anke

Subjects
SH2B1, Obesity, BMI, rs7498665, Mutation screen, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background The SH2B1 gene (Src-homology 2B adaptor protein 1 gene) is a solid candidate gene for obesity. Large scale GWAS studies depicted markers in the vicinity of the gene; animal models suggest a potential relevance for human body weight regulation. Methods We performed a mutation screen for variants in the SH2B1 coding sequence in 95 extremely obese children and adolescents. Detected variants were genotyped in independent childhood and adult study groups (up to 11,406 obese or overweight individuals and 4,568 controls). Functional implications on STAT3 mediated leptin signalling of the detected variants were analyzed in vitro. Results We identified two new rare mutations and five known SNPs (rs147094247, rs7498665, rs60604881, rs62037368 and rs62037369) in SH2B1. Mutation g.9483C/T leads to a non-synonymous, non-conservative exchange in the beta (βThr656Ile) and gamma (γPro674Ser) splice variants of SH2B1. It was additionally detected in two of 11,206 (extremely) obese or overweight children, adolescents and adults, but not in 4,506 population-based normal-weight or lean controls. The non-coding mutation g.10182C/A at the 3’ end of SH2B1 was only detected in three obese individuals. For the non-synonymous SNP rs7498665 (Thr484Ala) we observed nominal over-transmission of the previously described risk allele in 705 obesity trios (nominal p = 0.009, OR = 1.23) and an increased frequency of the same allele in 359 cases compared to 429 controls (nominal p = 0.042, OR = 1.23). The obesity risk-alleles at Thr484Ala and βThr656Ile/γPro674Ser had no effect on STAT3 mediated leptin receptor signalling in splice variants β and γ. Conclusion The rare coding mutation βThr656Ile/γPro674Ser (g.9483C/T) in SH2B1 was exclusively detected in overweight or obese individuals. Functional analyzes did not reveal impairments in leptin signalling for the mutated SH2B1.

Published
2012
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